A number of recent applications demonstrated the potential of radiolabeled aromatic aminoacids with Positron Emission Tomography (PET) for brain tumour imaging: the mechanism is similar to other metabolic substrate and it is based on their specific accumulation in neoplastic cells, probably linked to an increased expression of amino acid transporters, but not due to their incorporation in proteins.
Although fluorine-18 (109.7 min half-life) is the most interesting radionuclide for the preparation of PET radiopharmaceuticals, the labeling of amino acids with fluoride-18 is often difficult, particularly in aromatic positions (the use of the molecular F2, is on the contrary chemically unsuitable and is limited to a few PET centres provided of special equipment and cyclotron targets). An alternative way of labelling aromatic systems with fluorine-18 involves the introduction of a fluoroalkyl group to an aromatic position, rather than by direct labelling with a fluorine atom. In this class a promising molecule for its applicable in neurooncology is the O-(2-[18F]fluoroethyl)-L-tyrosine (FET), one the first 18F-labeled amino acids. The tracer demontrated high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging.
The main objective of this work is to demonstrate the feasibility of a novel approach for experimental BNCT, with a special focus to microimaging for the real assessment of the homogeneity and extent of accumulation of these class of aminoacid in tumour and surrounding healthy tissue. The goal of this study is then to use the FET to screen tumours lesions in experimental model with a small field of view PET, so called, micro PET. The micro PET-FET approach could lead to the assessment of the transport and the net influx and accumulation of FET molecule, as analogue to BPA. A correlation between BPA and FET pharmacokinetic, mainly linked to different affinities of transporters, could give numeric parameters useful for the assessment of boron loading in tumour and healthy tissues. The study present study was performed on implanted rats at the 3rd week after the tumour implantation (F98 glioma cell line).
In the frame of this project was developed a simple and convenient remote controlled, one-pot synthesis module for FET, based on an automated Gilson module (mod. Aspec XL) with opportune hardware and software modifications performed in our laboratories. The radiosynthesis was performed via no-carrier-added 18F-fluorination of N-trityl-O-(2-tosyloxyethyl)-L-tyrosine-tert-butylester with subsequent deprotection under nonaqueous conditions in the presence of tetra-butyl ammonium hydrogen carbonate/carbonate. Deprotection of the intermediate FET derivative is performed in presence of trifluoroacetic acid in trichloromethane followed by solid-phase extraction. The FET containing HPLC eluent can be used for studies without purifications. The radiochemical purity is not less than 98% and the typical uncorrected radiochemical yield is higher than 40%; the total synthesis time is less than 90 min.